tbuckley/cabot-search huggingface dataset:
Abstract 11027: SGK1 Inhibition and Attenuation of the Action Potential Duration in Re-Engineered Heart Cell Models of Drug-Induced QT Prolongation
Authors: David J Tester, Philip T Sager, Maengjo Kim, Sabindra Pradhananga, Samantha K Hamrick, Dinesh Srinivasan, Saumya Das, Michael J Ackerman
Journal: Circulation (2022)

Background: Drug-induced QT prolongation (DI-QTP) is a clinical entity in which administration of a HERG/I Kr blocker such as dofetilide prolongs the cardiac action potential duration (APD) at the cellular level and the QT interval clinically, and increases the risk for a potentially lethal, QT-triggered ventricular arrhythmia. There may be a role for inhibition of I NaL to counter DI-QTP. Recently, we have shown that inhibition of serum and glucocorticoid regulated kinase-1 (SGK1) reduces the APD90 in induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) from patients with LQT3 and ameliorates increases in I NaL . Objective: To test the efficacy of novel SGK1 inhibitors (SGK-I) in re-engineered cardiomyocyte models of dofetilide-induced APD prolongation. Methods: Normal iPSC-CMs were treated with dofetilide [5 nM] to produce a DI-QTP iPSC-CM model. The SGK1-I’s therapeutic efficacy for shortening the dofetilide-induced APD90 prolongation was compared to mexiletine. The APD90 values were recorded 4 hours after treatment using FluoVolt, a voltage-sensitive fluorescent dye. Results: The APD90 was significantly prolonged in normal iPSC-CMs treated with dofetilide (673 ± 8 ms with dofetilide vs 436 ± 4 ms with DMSO, p&lt;0.0001). While 10 μM mexiletine shortened the average APD90 of dofetilide-treated normal iPSC-CMs from 673 ± 4 ms to 563 ± 8 ms (46% attenuation, p&lt;0.0001), 30 nM of SGK-I shortened the APD90 from 673 ± 4 ms to 478 ± 10 ms (82% attenuation, p&lt;0.0001). Conclusions: Therapeutically inhibiting SGK1 effectively shortens the cardiomyocyte APD in a human heart cell model of DI-QTP. The novel SGK1 inhibitor normalized the pathological APD prolongation almost fully (&gt; 80%) in the iPSC-CM model treated with dofetilide. This pre-clinical data supports further development of this therapeutic strategy to counter and neutralize the threat of DI-QTP.
Abstract 10891: Artificial Intelligence Echocardiographic Detection of Right Ventricular Dysfunction in Patients With High-Risk Pulmonary Embolism
Authors: Brian C Hsia, Varsha Subramaniam, Supreet Singh, Ashton Lai, Rajeev Samtani, Solomon Bienstock, Steve Liao, Eric Stern, Gina LaRocca, Javier Sanz, stamatios lerakis, Lori Croft, Gregg Stone, Martin E Goldman
Journal: Circulation (2022)

Introduction: Patients (pts) with pulmonary embolism (PE) and right ventricular (RV) dysfunction have a worse prognosis. We previously validated a real-time artificial intelligence software (AI, LVivoRV®) which calculates RV fractional area changes (FAC), free wall strain (FWS), and tricuspid annular planar systolic excursion (TAPSE) from a single unedited, non-ultrasound agent-enhanced apical 4-chamber (A4C) TTE view. Hypothesis: AI-calculated TTE parameters of RV function will accurately identify pts with intermediate-high and high-risk PE that would otherwise have been identified by comprehensive physician assessment of all TTE parameters, physical exam and biomarkers (“physician assessment”). Methods: We retrospectively identified pts in whom both a TTE (60.7% with ultrasound contrast) and chest CTA were performed for PE evaluation (median 1 day between studies). Based on comprehensive physician assessments, pts were stratified by the 2019 ESC guidelines from low-risk to high-risk for PE mortality. The accuracy of AI-TTE thresholds for RV dysfunction (previously defined) to identify physician-assessed high-risk PE was examined. Results: Of the 107 pts, 66 (61.7%) had confirmed PE on CTA. By physician assessment, 28 of these 66 cases were classified as intermediate-high/high-risk PE. Across all AI-TTE parameters, the sensitivities and negative predictive values for intermediate-high/high-risk PE (n=28) ranged from 79-86% and 83-87% respectively (Table). In contrast, the specificities and positive predictive values ranged from 30-56% and 29-38%. Conclusions: A simple to use, fully automated, AI-based TTE assessment of RV dysfunction at the bedside identified ~85% of all cases that would otherwise have been identified as intermediate-high and high-risk PE by comprehensive physician assessment (although the false positive rate was high). Further studies are warranted to examine how best to integrate this AI into clinical care pathways.
Abstract 11018: The WATCH-IT Study: Wearable Device Use Among Primary Care and Cardiology Patients in a Large Healthcare System
Authors: Rachael A Venn, Mostafa Al-Alusi, Jeffrey M Ashburner, Steven Atlas, Yuchiao Chang, Patrick T Ellinor, Andrea Foulkes, Mia Grayson, Shaan Khurshid, David McManus, Daniel E Singer, Steven A Lubitz
Journal: Circulation (2022)

Introduction: Wearable devices such as smartwatches and fitness trackers are widely used. While marketed to consumers for general wellness, many devices measure physiologic parameters with implications for cardiovascular health. The prevalence of wearable device use in contemporary patient populations is unknown. We sought to 1) determine characteristics of current and prospective device users within a large healthcare system and 2) assess user interest in incorporating device data into the electronic health record for clinical research purposes. Methods: Participants were selected from a database of adults aged ≥ 18 years who received longitudinal primary or cardiac care at one of 11 hospitals within the Mass General Brigham network between 1/2010 and 7/2021. We identified living patients with an active electronic portal account for direct communication. Portal users were invited to complete a survey about use and medical applications of wearable devices. Multivariable logistic regression was used to identify factors associated with device use. Results: Between 11/2021 and 4/2022, 214,935 patients were contacted with 10,947 (5%) unique survey respondents. Rates of device use were similar among primary care (56%, n=4,739) and cardiology (53%, n=2,190) patients. Almost all non-users (97%, n=4,540) reported that they would use a device if not for cost. In a multivariable model, factors associated with device use included: age (odds ratio [OR] per 5-year increase 0.89, 95% CI [0.87,0.90]), female sex (1.19 [1.09, 1.29]), cardiac vs primary care (1.27 [1.16, 1.39]), median household income by zip code (OR per 1-standard deviation increase 1.10 [1.06, 1.15]), and better self-reported health (OR for “excellent” vs “poor” health 3.35 [2.27, 4.99]). Almost all users and potential users (96%, n=9,811) would share device data with researchers studying health outcomes. Conclusion: Among survey respondents, younger age, female sex, cardiac care, higher income, and better self-reported health were associated with wearable device use. Current and prospective device users are interested in sharing longitudinal data, which will enable further study of wearable devices and their role in care delivery, clinical outcomes, and health disparities.
Abstract 10996: Clinical Characteristics and Outcomes of Infective Endocarditis Among Intravenous Drug Abusers - A Single-Center Experience
Authors: Abdallah Almaghraby, Mahmoud Abdelnabi, Hoda Abdelgawad, Sahar Azab, Mohmaed Ayman Abdel-Hay
Journal: Circulation (2022)

Introduction: There are limited data regarding intravenous drug abuse (IVDA) associated with infective endocarditis (IE). The study aimed to compare IVDA to non-IVDA-associated IE regarding the differences in clinical profile, microbiology, echocardiography, and clinical outcomes among patients admitted with IE. Methods: 90 patients from January 2019 to December 2021 who met the Modified Duke ‘‘definitive’’ criteria for IE were included. Demographic, clinical, and laboratory data were collected. All patients underwent transthoracic echocardiography and transesophageal echocardiogram whenever indicated. In-hospital morbidity and mortality were reported. Results: Among the 90 patients included, 24 (26.7%) had a history of IVDA. IVDA-group were younger (27 vs 40 years, P&lt;0.0001), males (95.8% vs 69.7%, P=0.01), and more likely to have concomitant HCV and HIV infections compared to non-IVDA-group (50% vs 3%, P&lt;0.0001). Methicillin-resistant staphylococcus aureus (MRSA) percentage was higher in IVDA-group (54.2% vs 16.7%, P= 0.0004). Tricuspid value was the most common valve (79.2%) affected in IVDA-group whereas mitral followed by aortic valves were most commonly involved in non-IVDA-group (43.9% and 31.8% respectively). Embolic events at admission were more frequent in IVDA-group (83.3% vs 15.2%, P&lt;0.0001). Septic shock and embolic events (58.3%, 37.5% consecutively) are the most common causes of in-hospital morbidity among IVDA-group. In-hospital mortality was significantly higher among IVDA-group compared to non-IVDA-group (58.3% vs 25.8%, P=0.04). Conclusion: The demographic, microbiological, and echocardiographic profile is quite different in IVDA and non-IVDA-group. Larger studies are required to confirm these data, especially in low- and middle-income countries.
Abstract 10931: Impact of Atrial Fibrillation Type (paroxysmal vs. Non-paroxysmal) on Long-Term Clinical Outcomes: The Raffine Registry Subanalysis
Authors: Hideki Wada, Katsumi MIYAUCHI, Satoru SUWA, Sakiko Miyazaki, Hidenori Hayashi, Tadashi MIYAZAKI, Masataka Sumiyoshi, YUJI NAKAZATO, Tohru Minamino, Hiroyuki Daida
Journal: Circulation (2022)

Background: Type of atrial fibrillation (AF) (paroxysmal or non-paroxysmal) is important for determining the therapeutic management. However, prognostic impact of AF type on incidence of cardiovascular events remains uncertain. Methods: We investigated patients with AF who were selected from an observational, multicenter, prospective registry (RAFFINE) comprising 4 university hospitals and 50 general hospital / clinics in Japan between 2013 and 2015. In this subanalysis of the RAFFINE trial, patients were divided into 2 groups according to their AF pattern at the time of enrollment. The primary outcome was composite of all-cause death, ischemic stroke, and heart failure related hospitalization. Results: Among 3,845 patients, 1,472 (38.3%) and 2,373 (61.7%) were paroxysmal and non-paroxysmal AF, respectively. Patients with non-paroxysmal AF were older, higher CHADS 2 score and had higher prevalence of comorbidities compared with those with paroxysmal AF. During a median follow-up of 3.7 years, 681 (17.7%) primary endpoints were identified. Cumulative incidences of primary endpoint were significantly higher in non-paroxysmal AF group (log-rank p&lt;0.0001, Figure ), however, rates of bleeding events were not significantly different between groups. Multivariate cox hazard analysis showed that non-paroxysmal AF had significantly higher risk of cardiovascular events compared with paroxysmal AF (adjusted hazard ratio: 1.38, 95% confidence interval 1.17-1.64, p = 0.0002). Conclusions: In the RAFFINE registry, non-paroxysmal AF was significantly associated with worse clinical outcomes among AF patients. Long-term clinical outcomes might be improved if the transition paroxysmal to non-paroxysmal AF can be prevented.
Abstract 10590: Detection of Cardiac Attr Amyloidosis in a Real-World Hf Population by Natural Language Processing Guided Automated Data Extraction From Electronic Health Records
Authors: Monika Beles, Dries Hens, Imke Masuy, sofie verstreken, Ward Heggermont, Riet Dierckx, Jozef Bartunek, Marc Vanderheyden
Journal: Circulation (2022)

Background: As cardiac aTTR amyloidosis(aTTR-CM) is frequently underdiagnosed and missed, improved screening to enhance earlier diagnosis of the disease is essential. Recent observations have demonstrated that clinical clues related to the presence of aTTR-CM and additional predisposing or associated medical conditions derived from machine learning(ML) models may provide a systematic framework to increase the suspicion of aTTR-CM in heart failure(HF) pts. Objectives: The present study was set up to explore the use of a systematic framework to diagnose aTTR-CM in a real-world HF population. Methods: Between 2014 and 2018, 3035 HF pts (Age:74 ± 12 years; EF: 45 ± 19 %, male: 50 %) consecutively referred to a community HF clinic were assessed. Using targeted disease-specific electronic health record (EHR) models (Natural language processing/ LynxCare Inc., Leuven, Be) the prevalence and odds ratios for cardiac, non-cardiac, and combinations of both cardiac and non-cardiac phenotypes predictive for aTTR-CM were assessed. Results: 101 pts((Age: 78.57 ± 9.17 years; EF 46 ±15 %, male: 40% ) were diagnosed with aTTR-CM. Besides HF and cardiomyopathy-related phenotypes, atrial fibrillation was the strongest cardiac predictor for aTTR-CM(prevalence:76 %, OR 2.95, 95% CI= 2.10, 4.14) whereas the strongest non-cardiac predictor was carpal tunnel syndrome(prevalence :21 %, OR 6.55, 95% CI= 7.21, 5.90). The combination of heart block, joint disorders, and combined systolic and diastolic HF was the highest combined phenotype in aTTR-CM(prevalence:16 %, ORR 2.63, 95% CI = 0.96, 3.28). Conclusion: On top of well-known diagnoses and phenotypes unique combinations of cardiac and non-cardiac phenotypes predict aTTR-CM In a real-world HF population. Therefore, if successfully employed in the EHR this strategy may identify aTTR-CM pts and lead to earlier detection of it by raising the suspicion of the diagnosis in HF pts.
Abstract 10420: Spontaneous Coronary Artery Dissection in a Young Man Taking Sumatriptan
Authors: Eric Hirsch, Parrykumar Mendapara, Matthew Akiyama
Journal: Circulation (2022)

Introduction: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome. There is an approximate 9:1 female predominance, and commonly cited risk factors include fibromuscular dysplasia, pregnancy, and cocaine use. We present a case of SCAD in a young man with migraines and triptan use, initially misdiagnosed as panic disorder. Case: A 25-year-old man with a history of migraines treated with sumatriptan presented with several months of intermittent chest pain and syncopal episodes. He had been evaluated in an emergency department at the onset of symptoms and diagnosed with panic disorder. His EKG now showed Q waves in leads V1-V2 and T wave inversions in leads I and AVL. Serial troponins were stable at 0.04 ng/mL. An echocardiogram showed left ventricular apical ballooning and large thrombus. Left heart catheterization revealed significant stenosis of the proximal LAD and 50% stenosis of the mid LAD (Fig. 1A). A follow-up CT angiogram showed intimal thickening and perivascular fat stranding in the proximal and mid LAD, confirming a diagnosis of SCAD (Fig. 1B). A full-body CTA showed no additional aneurysm or dissection. Inflammatory markers and autoimmune serologies were negative. Urine toxicology was negative for cocaine or amphetamines. Given an otherwise unrevealing workup, migraines and triptan use were identified as the significant risk factors for SCAD. He was discharged with clopidogrel, warfarin, and metoprolol and counseled against further use of triptans Discussion: Multiple studies have reported increased prevalence of SCAD in patients with migraines, particularly those using triptans. This phenomenon likely relates to stimulation of 5-HT1B and 5-HT1D receptors in the coronary vasculature. Greater recognition of SCAD and its risk factors is essential for timely diagnosis and treatment, particularly in young patients whose chest pain may be falsely attributed to non-cardiac causes.
Abstract 10876: Thrombo-Inflammatory Biomarkers in Pulmonary Embolism as Stratified in Cancer and Non-Cancer Patient Groups
Authors: Fakiha Siddiqui, Amir Darki, Debra A Hoppensteadt, Bulent Kantarcioglu, Alfonso J Tafur, Jawed Fareed, Manuel Monreal
Journal: Circulation (2022)

Introduction: The multifactorial and complex pathophysiology of pulmonary embolism (PE) involves dysregulation of hemostatic system including fibrinolytic imbalance, endothelial compromise, and generation of thrombotic mediators, along with cellular defects and hemodynamic derangement. Cancer is prevalent in PE patients and is considered an added risk factor for the adverse outcomes. Thrombo-inflammatory biomarkers profiling provide means to risk stratify PE patients. Hypothesis: This study aimed to profile several of these biomarkers in normal and PE patients and to further demonstrate any potential difference between cancer and non-cancer patients. Methods: Four hundred patients of 18 years or older age, were included through enrolment in conjunction with IRB approved project by the pulmonary embolism response team (PERT) registry. Diagnosis of PE was confirmed by computed tomography (CT), angiography or ventilation perfusion imaging. Blood samples were drawn with in 24 hours of confirmed diagnosis of acute PE. Control plasma samples were obtained from 50 healthy individuals. All plasma samples were analyzed for D-Dimer, PAI-1 antigen, tPA, TAFI-a, vWF, CRP, troponin and IL-6 were measured by ELISA methods. Microparticles were measured using a chromogenic functional method. Individual biomarkers were compared to normal plasma and further stratified into cancer and non-cancer. Results: All the individual biomarkers exhibited up to 50-fold elevation in PE patients compared to normal groups. D-Dimer and CRP showed the most pronounced increase. When the PE group stratified into cancer and non-cancer patients, most of the biomarkers except D-Dimer and microparticles showed varying degree of modest elevation in the cancer group. vWF, IL6 and microparticles levels were found to be significantly different in the cancer group (p&lt;0.050). Conclusions: These studies demonstrate that thrombo-inflammatory biomarkers are upregulated in PE patients. Furthermore, PE patients with cancer exhibit amplified levels of some of the markers suggesting the increased severity of pathogenesis involving thrombo-inflammatory mechanisms.
Abstract 10046: Type I Kounis Syndrome Induced by Echocardiography Contrast Agent Sulfur Hexafluoride
Authors: Soroush Nomigolzar, Sara Khederzadeh, Alisha Baggett, Meghana Vallabhaneni, Ahmed Younes
Journal: Circulation (2022)

Background: Acute coronary syndrome (ACS) and anaphylaxis are both medical emergencies that require prompt intervention. ACS occurring in the setting of hypersensitivity reaction, presumably secondary to inflammatory mediator release, is called Kounis Syndrome (KS). There are three subtypes of KS: Type I (clean coronary arteries), type II (pre-existing CAD), and type III (in-stent restenosis). Allergens such as medications, insect bites, foods, and contrast media have been found to result in KS. However, to our knowledge, there is only one reported case of KS induced by sulfur hexafluoride (echocardiography enhancing agent), which was categorized as KS type III. Here, we report a case of allergic reaction to this agent causing KS type I. Case Presentation: A 74-year-old woman with a history of anaphylaxis (to penicillin and cephalosporins), provoked pulmonary embolism (PE), hypertension, and hypothyroidism presented with dyspnea and was found to have bilateral subacute PE on CTA chest. She was started on a heparin drip and subsequently underwent echocardiography which showed normal RV size, systolic function, and LVEF with no wall motion abnormalities. However, shortly after receiving the sulfur hexafluoride agent, the patient was noted to be somnolent, hypotensive, and diaphoretic. Allergic reaction to the contrast was suspected and she received methylprednisolone, diphenhydramine, and famotidine. STAT EKG revealed ST elevation in inferior leads and the patient subsequently underwent cardiac catheterization which showed no evidence of significant obstructive disease. The patient remained hemodynamically stable throughout the remainder of her admission and was transitioned from heparin drip to apixaban prior to discharge. Discussion: In conclusion, allergic reactions could lead to an acute coronary syndrome with non-obstructive coronaries. As a result, it is crucial to consider KS as a differential. Figure 1 - ST elevations in the inferior leads
Abstract 10135: Mortality From Birth to Young Adulthood Among Individuals With Congenital Heart Defects: Results From the Congenital Heart Survey to Recognize Outcomes, Needs, and Well-Being
Authors: Karrie F Downing, Wendy N Nembhard, CHARLES E ROSE, Matthew Oster, Scott E Klewer, Anthony Goudie, Jennifer Andrews, Sherry Farr
Journal: Circulation (2022)

Introduction: Limited information exists on long-term mortality of individuals with congenital heart defects (CHD) in the United States. Our objective was to evaluate mortality and related factors among a population-based sample of individuals with CHD born in three U.S. locations. Methods: Birth defects surveillance system data on individuals with CHD born between 1980-1997 in Arkansas, Arizona, and Atlanta, Georgia, for the Congenital Heart Survey to Recognize Outcomes, Needs, and well-beinG (CH STRONG) were linked to death records through 2015. Survival probability was estimated using Kaplan-Meier survival curves. For those who survived past one year of age, associations between age at death up to 35 years and characteristics at birth were assessed by adjusted hazards ratios and 95% confidence intervals (CIs) from multivariable Cox proportional hazards models. Standardized mortality ratios (SMRs) and CIs comparing observed to expected deaths based on age-, sex-, year-, race/ethnicity-, and site-specific population mortality rates from the National Vital Statistics System (NVSS) data were calculated. Results: Of 11,333 included individuals from CH STRONG, 9,630 (85%) survived to one year of age; of those, probability of survival to age 35 years was 95.8%. Hazard ratios for death up to age 35 years were elevated for those with severe defects, non-cardiac congenital anomalies, and maternal race other than non-Hispanic (NH) white (Figure). The SMR comparing CH STRONG to NVSS was 4.6 (CI: 4.3, 5.0); SMRs remained elevated when limiting to NH white (SMR=4.1, CI: 3.7, 4.5), NH Black (SMR=4.6, CI: 3.9, 5.4), males (SMR=3.6, CI: 3.3, 4.1) and females (SMR=6.8, CI: 6.0, 7.6). Conclusions: Individuals with CHD who survived to 1 year of age had 95.8% survival to age 35 years, with their risk of mortality 4.6 times that of the general population. People with severe defects, non-cardiac congenital anomalies, and maternal race other than NH white had the greatest mortality risk.